In order to understand
adverse health effects of environmental agents it is essential to understand
basic principles and definitions of toxicology.

Pharmacokinetics
refers to the quantitative time course of toxins in the body and depends
on absorption, distribution, biotransformation, and excretion.

Absorption
of toxic chemicals by exposed individuals can occur via three different
routes of entry.These include inhalation of fumes, vapors,
and particulates into the respiratory tract; ingestion into the
gastrointestinal tract; and dermal (skin) absorption of a liquid.
Logically, the more volatile the compound, the more likely it is to be
inhaled. Ingestion occurs in environmental situations, including water
contamination and accidental or intentional ingestion. The more fat-soluble
a compound, the more likely it is to be absorbed into the body by all
three routes.

Chemical toxins can
exert their effects at the point of entry with direct, local irritation;
others are absorbed into the bloodstream and act at distal (distant) sites
either by 1) direct toxicity to a susceptible target organ, 2)
by sensitization or allergy, generally after multiple episodes
of exposure, causing a reaction manifested by any or all of the following:
skin rash, bronchospasm (an asthma-like picture), hypotension, and sudden
death, or 3) by an idiosyncratic reaction which has to do with
susceptibility based on the individual's genetic make-up; this type of
reaction may initiate a cascade of biochemical and micro-anatomical changes
that manifest in a toxic syndrome.

The distribution
of a chemical toxin in the body is based on the charge/fat solubility,
the size of the molecule or ion, and its interaction with naturally occurring
enzymes, protein carriers and other chemicals in the body. A toxin's distribution
greatly influences its toxicity. For example, some chemicals are absorbed
by organs they do not damage(like lead in bone), thereby reducing their
effective circulating dose in the body. Others concentrate in their target
organ, where they exert their adverse effects.

Many chemicals undergo
biotransformation in the body by existing enzyme systems. This process
can render them more or less toxic, and can form charged or uncharged
molecular structures which determine how a given chemical will be handled
by the body. Fat-soluble molecules may bioaccumulate, or concentrate,
in fatty tissues of the body where quantity can grow over time; a stressor,
such as rapid weight loss, can cause a sudden increase in circulating
levels of toxicants in the body.

The more rapidly a
chemical is eliminated from the body, most frequently in the kidney
or GI tract, the less time it has to exert its toxic effect. The elimination
half-life refers to the amount of time required for excretion of
half the internal exposure concentration. Fat soluble substances, which
tend to be absorbed fatty tissue, are less available for excretion.
They may be excreted slowly over time, and only if transformed to a water-soluble
product.

Acute toxicity
refers to short-term adverse health effects; chronic toxicity refers
to exposure over a period of time which results in delayed toxic manifestations.
The occurrence of the latter is presumably due to accumulation of dose
over time or to the eventual over-ride of the host's (exposed individual's)
natural defense mechanisms.

The quantity and duration
of exposure determine the dose assumed by the host. In general,
there is a dose-response relationship between toxin exposure and
symptom or disease manifestation, i.e., the greater the dose, the more
likely an adverse effect will be seen (and the more severe the effect,
as the dose increases). For many chemicals, there appears to be a threshold,
frequently expressed in milligrams (or quantity) of toxin per kilogram
of the host's body weight, above which toxic effects are first manifested.
This threshold value is best described for pharmaceuticals which have
been carefully tested in animal models as well as humans; for industrial
or environmental chemicals, this threshold is derived from animal studies
and from case reports of intoxicated humans where exposure levels have
been known. There may not be a threshold below which carcinogenicity (cancer-causing
mutations) will not occur.